Country for PR: United Kingdom
Contributor: PR Newswire Europe
Wednesday, December 07 2022 - 17:00
Pharming announces publication of data from Phase 3 Study of leniolisib in patients with APDS in ASH's Blood
LEIDEN, Netherlands, Dec. 7, 2022 /PRNewswire-AsiaNet/--

Leniolisib was well tolerated and significant improvement over placebo was 
notable in the co-primary endpoints, reflecting a favorable impact on patients' 
immune dysregulation and deficiency

The peer-reviewed publication heightens international understanding of APDS, a 
rare and recently characterized immunodeficiency

Pharming Group N.V. ("Pharming" or "the Company") (EURONEXT Amsterdam: PHARM) 
(Nasdaq: PHAR) announces today that the positive results of a Phase 3 clinical 
trial of the investigational drug leniolisib, an oral, selective 
phosphoinositide 3-kinase delta (PI3K[delta]) inhibitor, in adult and 
adolescent patients with activated phosphoinositide 3-kinase delta syndrome 
(APDS), a rare primary immunodeficiency, have been published in Blood,1 the 
peer-reviewed international medical journal of the American Society of 
Hematology ( 
). Data from this study was previously announced on February 2, 2022.

The paper, entitled 'Randomized, Placebo-Controlled, Phase 3 Trial of 
PI3K[delta] Inhibitor Leniolisib for Activated PI3K[delta] Syndrome', outlined 
results from the multinational, triple-blind, placebo-controlled, randomized 
clinical trial, which enrolled 31 patients with APDS aged 12 years or older. 
Patients were randomly assigned in a 2:1 ratio to receive 70 mg leniolisib or 
placebo twice daily for 12 weeks. Improvement over placebo was significant in 
the co-primary endpoints which evaluated reduction in lymph node size and 
increase in naive B cells, reflecting the impact on immune dysregulation and 
correction of immunodeficiency in these patients, respectively. The adjusted 
mean change (95% CI) between leniolisib and placebo for lymph node size was 
-0.25 (-0.38, -0.12; P=0.0006; N=26) and for percentage of naive B cells was 
37.30 (24.06, 50.54; P=0.0002; N=13). Leniolisib was well tolerated, and fewer 
patients receiving leniolisib reported study treatment-related adverse events 
(mostly grades 1-2) compared to those receiving placebo (23.8% vs 30.0%).

Vicki Modell, co-founder of the Jeffrey Modell Foundation, an international, 
non-profit, organization dedicated to helping individuals and family members 
affected by primary immunodeficiency disorders, commented: 

"Pharming continues to provide significant support for the immunodeficiency 
community. The Jeffrey Modell Foundation is dedicated to early diagnosis and 
finding meaningful treatments for primary immunodeficiency, and we are acutely 
aware of the challenges faced by people with APDS. The publication of study 
results in this patient population in such a distinguished and widely read 
journal advances these goals."

Anurag Relan, MD, MPH, Chief Medical Officer of Pharming, commented:

"As we continue to seek a better understanding of APDS as a recently 
characterized rare disease, we remain committed to sharing our findings with 
researchers and doctors around the world. With this commitment in mind, we are 
pleased the results of this Phase III clinical trial in leniolisib have been 
published in the flagship journal of the American Society of Hematology.

The APDS patient population, and their families, have lived with unmet needs 
and without targeted therapies, and the publishing of this study is an integral 
step in improving the patient journey for this community. We are proud to share 
these results which demonstrated leniolisib to be a well-tolerated, targeted 
therapy for APDS. We thank all of our study participants and investigators for 
their efforts and the essential role they played in the development of 

About Activated Phosphoinositide 3-Kinase [delta] Syndrome (APDS)

APDS is a rare primary immunodeficiency that affects approximately 1 to 2 
people per million. APDS is caused by variants in either of two genes, PIK3CD 
or PIK3R1, that regulate maturation of white blood cells. Variants of these 
genes lead to hyperactivity of the PI3K[delta] (phosphoinositide 3-kinase 
delta) pathway.2,3 Balanced signaling in the PI3K[delta]  pathway is essential 
for physiological immune function. When this pathway is hyperactive, immune 
cells fail to mature and function properly, leading to immunodeficiency and 
dysregulation.2,4 APDS is characterized by severe, recurrent sinopulmonary 
infections, lymphoproliferation, autoimmunity, and enteropathy.5,6 Because 
these symptoms can be associated with a variety of conditions, including other 
primary immunodeficiencies, people with APDS are frequently misdiagnosed and 
suffer a median 7-year diagnostic delay.7 As APDS is a progressive disease, 
this delay may lead to an accumulation of damage over time, including permanent 
lung damage and lymphoma.5-8 The only way to definitively diagnose this 
condition is through genetic testing.

About Leniolisib

Leniolisib is a small-molecule inhibitor of the delta isoform of the 110 kDa 
catalytic subunit of class IA PI3K. PI3K[delta]  is expressed predominately in 
hematopoietic cells and is essential to normal immune system function through 
conversion of phosphatidylinositol-4-5-trisphosphate (PIP2) to 
phosphatidylinositol-3-4-5-trisphosphate (PIP3). Leniolisib inhibits the 
production of PIP3 and PIP3 serves as an important cellular messenger 
activating AKT (via PDK1) and regulates a multitude of cell functions such as 
proliferation, differentiation, cytokine production, cell survival, 
angiogenesis, and metabolism. Unlike PI3K[alpha] and PI3K[beta], which are 
ubiquitously expressed, PI3K[Gamma] and PI3K[delta]  are expressed primarily in 
cells of hematopoietic origin. The central role of PI3K[alpha] in regulating 
numerous cellular functions of the adaptive immune system (B-cells and, to a 
lesser extent, T cells) as well as the innate immune system (neutrophils, mast 
cells, and macrophages) strongly indicates that PI3[delta] is a valid and 
potentially effective therapeutic target for immune diseases such as APDS. To 
date, leniolisib has been well tolerated during both the Phase 1 first-in-human 
trial in healthy subjects and the Phase II/III registration-enabling study in 
patients with APDS.

About Pharming Group N.V.

Pharming Group N.V. (EURONEXT Amsterdam: PHARM) (Nasdaq: PHAR) is a global 
biopharmaceutical company dedicated to transforming the lives of patients with 
rare, debilitating, and life-threatening diseases. Pharming is commercializing 
and developing an innovative portfolio of protein replacement therapies and 
precision medicines, including small molecules, biologics, and gene therapies 
that are in early to late-stage development. Pharming is headquartered in 
Leiden, Netherlands, and has employees around the globe who serve patients in 
over 30 markets in North America, Europe, the Middle East, Africa, and 

For more information, visit and find us on LinkedIn 

Forward-Looking Statements

This press release may contain forward-looking statements. Forward-looking 
statements are statements of future expectations that are based on management's 
current expectations and assumptions and involve known and unknown risks and 
uncertainties that could cause actual results, performance, or events to differ 
materially from those expressed or implied in these statements. These 
forward-looking statements are identified by their use of terms and phrases 
such as "aim", "ambition", "anticipate", "believe", "could", "estimate", 
"expect", "goals", "intend", "may", "milestones", "objectives", "outlook", 
"plan", "probably", "project", "risks", "schedule", "seek", "should", "target", 
"will" and similar terms and phrases. Examples of forward-looking statements 
may include statements with respect to timing and progress of Pharming's 
preclinical studies and clinical trials of its product candidates, Pharming's 
clinical and commercial prospects, and Pharming's expectations regarding its 
projected working capital requirements and cash resources, which statements are 
subject to a number of risks, uncertainties and assumptions, including, but not 
limited to the scope, progress and expansion of Pharming's clinical trials and 
ramifications for the cost thereof; and clinical, scientific, regulatory and 
technical developments. In light of these risks and uncertainties, and other 
risks and uncertainties that are described in Pharming's 2021 Annual Report and 
the Annual Report on Form 20-F for the year ended December 31, 2021, filed with 
the U.S. Securities and Exchange Commission, the events and circumstances 
discussed in such forward-looking statements may not occur, and Pharming's 
actual results could differ materially and adversely from those anticipated or 
implied thereby. All forward-looking statements contained in this press release 
are expressly qualified in their entirety by the cautionary statements 
contained or referred to in this section. Readers should not place undue 
reliance on forward-looking statements. Any forward-looking statements speak 
only as of the date of this press release and are based on information 
available to Pharming as of the date of this release. Pharming does not 
undertake any obligation to publicly update or revise any.


[1] Rao VK, et al. Blood. 2022.
[2] Lucas CL, et al. Nat Immunol. 2014;15:88-97.
[3] Elkaim E, et al. J Allergy Clin Immunol. 2016;138(1):210-218.
[4] Nunes-Santos C, Uzel G, Rosenzweig SD. J Allergy Clin Immunol. 
[5] Coulter TI, et al. J Allergy Clin Immunol. 2017;139(2):597-606.
[6] Maccari ME, et al. Front Immunol. 2018;9:543.
[7] Jamee M, et al. Clin Rev Allergy Immunol. 2019;May 21.
[8] Condliffe AM, Chandra A. Front Immunol. 2018;9:338.

For further public information, contact:

Pharming Group, Leiden, The Netherlands
Michael Levitan, VP Investor Relations & Corporate Communications
Heather Robertson, Investor Relations & Corporate Communications Manager

FTI Consulting, London, UK
Victoria Foster Mitchell/Alex Shaw/Amy Byrne
T: +44 203 727 1000

LifeSpring Life Sciences Communication, Amsterdam, The Netherlands
Leon Melens
T: +31 6 53 81 64 27

Ethan Metelenis
T: +1 (917) 882 9038

Dan Caley
T: +44 (0) 787 546 8942

Logo -

Source: Pharming Group NV